The concept of a “polypill” is receiving growing attention to prevent cardiovascular disease. Yet similar if not overall higher benefits are achievable with regular exercise, a drug-free intervention for which our genome has been haped over evolution. Compared with drugs, exercise is available at low cost and relatively free of adverse effects. We summarize epidemiological evidence on the preventive/therapeutic benefits of exercise and on the main biological mediators involved.

Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people.

There is a pandemic of physical inactivity that appears to parallel the widespread prevalence of cardiovascular disease (CVD). Yet, regular physical activity (PA) and exercise can play an important role not only in primary cardiovascular prevention but also in secondary prevention. This review discusses some of the main cardiovascular effects of PA/exercise and the mechanisms involved, including a healthier metabolic milieu with attenuation of systemic chronic inflammation, as well as adaptations at the vascular (antiatherogenic effects) and heart tissue (myocardial regeneration and cardioprotection) levels. The current evidence for safe implementation of PA and exercise in patients with CVD is also summarized.